The related art discloses various methods used in the past for inducing brain seizures in patients for the treatment of certain neurologic and psychiatric disorders ("neuropsychiatric disorders"), particularly certain types of psychotic depression. For example, brain seizures may be induced in human patients by the injection of chemical convulsant agents (pentylenetetiazol), the inhalation of gaseous convulsant agents (e.g. flurothyl), or by the application of electric currents to the scalp in a procedure termed electroconvulsive therapy (ECT), sometimes referred to as "shock therapy." Only ECT is still used to induce therapeutic brain seizures.
In addition, often various pharmacological agents (drugs) such as imipramine, lithium, bromazepam, etc. have been used to treat psychotic depression. However, sometimes such pharmacological agents have adverse side effects or are not effective.
In a present method of ECT, a pulsed or sinusoidal current of constant amperage or constant voltage is applied through electrodes to the patient's head for a period of 1-10 seconds. There are various possible drawbacks to ECT, however. These drawbacks include:
(1) The electrical resistance of the skull to the passage of current greatly attenuates the amount of current that actually reaches the brain. The rest of the current is shunted through the skin and scalp. Increasing the amount of current applied to the head, to reach the minimum required to induce seizures, may result in burns to the scalp and skin from the shunted current. PA1 (2) Because the direct passage of electric current through the relatively high-impedance skin during ECT can cause skin burns, the doctor must reduce the impedance of the electrode-to-skin interface by first cleansing the skin, then wiping the skin dry, and applying conductive gel over the metal electrode surfaces and their application sites on the skin. Special effort is then required of the doctor to ensure that the metal disc electrodes are applied firmly to the skin, either by holding them in place with a rubber headstrap or holding them with manually applied non-conductive electrode handles. Alternatively, self-adherent, solid-gel disposable stimulus electrodes can be used, after first cleansing the skin and then wiping the skin dry. Metal disc electrodes, rubber headstraps, non-conductive electrode handles, and disposable self-adherent stimulus electrodes are all costly to purchase and time-consuming to maintain and use. PA1 (3) The attenuated current that finally penetrates the skull is often capable only of stimulating seizures over the surface (cortex) of the brain. These seizures must then spread by secondary means to the deeper brain structures where the therapeutic effects of a seizure are believed to occur. Often these secondary means of spread are insufficient to induce therapeutic remission of the disorder. PA1 (4) It has been reported that memory loss may accompany the passage of current through the temporal lobes of the brain. PA1 (5) Leakage currents from defective equipment may reach the patient through the electrodes. Such leakage currents are dangerous to patients with cardiac arrhythmias or pacemakers. This requires that the ECT equipment undergo regular, and expensive, calibration checks. PA1 (6) The negative stigma to much of the public to the phrase "shock therapy" causes many patients to refuse the treatment even though it would be beneficial to them. PA1 (7) All convulsive therapies, including ECT, induce generalized brain seizures that stimulate superficial and deep subcortical brain structures indiscriminately. In some neuropsychiatric disorders, however, it is only the deep brain structures (e.g. the diencephalon) that functions abnormally and therefore requires stimulation. PA1 (8) Generalized seizures have hemodynamic consequences (hypertension, tachycardia, increased intracranial pressure) that can present unacceptable risks to patients with pre-existing cerebral, cardiovascular, or cerebrovascular conditions (e.g. myocardial infarction, hypertension, stroke, brain tumor). These result from the spread of seizure activity into brain areas that control cardiovascular excitation, such as the medulla. PA1 (9) Use of costly professional personnel and expensive facilities are usually required for ECT administration. Needed and billed services include anesthesiologist consultations and services, hospital pharmacy fees for solutions and anesthetics, and hospital fees for use of a treatment procedure room. PA1 (1) The low energy current often fails to penetrate the bony skull in sufficient dosage to stimulate the deep subcortical brain structures that are believed to require the most stimulation. Any increase in the amount of current used increases the risk of the undesirable side-effects of generalized brain seizures that occur in ECT. PA1 (2) The electric currents used in NCEST (and also in ECT) tend to diffuse through the brain as a volume conductor. This means the current is dispersed fairly evenly throughout the brain and cannot be focused, or concentrated, in a specific deep brain region, such as the diencephalon, to cause a therapeutic stimulation in just that region. PA1 (3) Even the low energy currents used in NCEST may cause painful sensations in the skin and scalp that require the use of general anesthesia. The use of general anesthesia has been reported to cause mortality rates of approximately 0.001% due to gastric paresis with vomiting and aspiration pneumonitis, hypotensive cardiovascular collapse, or laryngospasm causing cerebral anoxia. PA1 1. It does not apply electric currents to the skin and so does not expose the subject to the risk of skin burns. PA1 2. Its magnetic fields require no direct contact with the skin, so that time-consuming skin preparation is unnecessary and costly stimulus electrodes or accessories are not required. PA1 3. There is no attenuation of the therapeutic stimulus before it reaches the deep brain structures because the bony skull does not significantly impede the transmission of magnetic fields. The intended strength electrical field current is directly induced in the brain region specified with NCMST. PA1 4. Because magnetic fields can be oriented in three dimensions, to induce focused electrical field currents in deep brain structures, there is no necessity for the spread, and consequent attenuation, of brain tissue excitation from superficial to deep structures during the application of such magnetic fields. PA1 5. It does not pass external electrical currents through the temporal lobes and consequently its use would not cause the same deleterious memory effects that have been reported in some cases from ECT. PA1 6. It does not apply electric currents to the skin and, consequently,the patient receiving NCMST does not experience the painful electrical sensations or shocks possible with ECT. This avoids the need for general anesthesia which has morbid and mortal risks. PA1 7. It requires no patient electrical or mechanical contact. The patient receiving NCMST is not subjected to the risks of leakage currents and there is no need for costly and time-consuming leakage current tests and impedance tests of the device. PA1 8. No electrical stimuli or shocks are applied to the subject's head and the intent is not to induce a seizure. The method of NCMST is not "shock therapy", thus avoiding the prejudicial implications, to some members of the public, to this term.
NCEST (non-convulsive electrical stimulation therapy) applies a pulsed current of constant low amperage or voltage. This stimulates surface and deep brain structure, but does not induce brain seizures because of the low energy used. When used at particularly low current it may act by direct stimulation of tissues only outside the central nervous system (CNS) and only indirect stimulation of the CNS. However, NCEST suffers from many of the drawbacks that appear in ECT and, in addition:
The inventor's prior U.S. Pat. No. 5,769,778 describes a method for stimulating surface, intermediate, or deep brain structures by the application of pulsed magnetic fields near the outside surface of the patient's head, e.g., transcranial magnetic stimulation therapy ("TMST"). The generated magnetic fields induce corresponding electrical fields in surface and deep brain structures, thereby depolarizing nerve cells and raising their level of excitation closer to the point of neuronal discharge. In the embodiment designated non-convulsive magnetic stimulation therapy (NCMST), the intended therapeutic agent is low-energy excitation of one or more brain structures without the induction of a generalized brain seizure.
Non-convulsive magnetic stimulation therapy (NCMST) has the following advantages compared to ECT:
Unfortunately, the application of NCMST may involve the risk, to the patient, of inducing a convulsive seizure, e.g. unplanned grand mal seizure. Individuals would be expected to differ in the amount of NCEST, i.e., the strength and duration of the magnetic fields, they could successively undergo without being thrown into seizure. Such a convulsive seizure may be frightening to the patient, and both physically and psychologically damaging to him. It may cause the patient to withdraw from further NCMST.
During the procedure of non-convulsive magnetic brain stimulation (NCMST) it is essential to avoid the induction of a seizure in the patient, especially because no muscle-relaxant drugs are given with NCMST (as they are with ECT). Such unmodified seizure induction may produce several noxious stresses, including cerebral hypoxia, cardiac ischemia, cyanosis, falling and other mechanical consequences of abrupt unconsciousness, elevation of intracranial pressure, two-fold elevation of cerebral blood flow, increase of blood pressure and heart rate, depletion of available metabolic energy by protracted seizure, and combination effects that exceed the sum of components such as neurotoxicity from simultaneous hypoxia and energy depletion. In addition, stresses from the muscular activity of unmodified grand mal seizures can lead to bone fractures, joint dislocations, aspiration pneumonitis, tooth fractures, tongue bites, and muscle sprains. Injuries can also result from seizure-induced confusion and disturbances of behavior. The risks of such injuries simply make unmodified grand mal seizures undesirable and their prevention a compelling priority.
One method to avoid convulsions, an adverse side effect, is to lower the stimulus dosage. But individuals, possibly because of gender, weight, age, physical condition, past brain injury history, and other factors, may widely differ in the amount of NCMST with which they can be treated, without convulsions. That amount of NCMST is presently not directly predictable and there is presently not even a data base of subjects treated with NCMST to arrive at a safe and yet effective amount. If the amount of NCMST is lowered to be perfectly safe (without causing convulsions) for all individuals, it is likely to be so low as to be ineffective for most patients.
There is presently no device or method which is commercially available to provide, on an individual-by-individual basis, the proper dosage of NCMST, i.e., a dosage which is sufficiently low to be safe (not induce seizure) and yet sufficiently high to be effective.
In U.S. Pat. No. 5,743,860 entitled "Apparatus And Method For Epileptic Seizure Detection Using Non-Linear Techniques," a patient's brain waves are analyzed using EEG (electroencephalograph) and chaotic time/series analysis to determine if a trend in non-linear measure indicates a seizure.
In U.S. Pat. No. 5,349,962 entitled "Method And Apparatus For Detecting Epileptic Seizures," an EEG and EMG (electromyograph) provide signals to signal processors. If either the EEG or EMG is above a window threshold it is an indication of seizure.
In U.S. Pat. No. 5,311,876, entitled "Automatic Detection Of Seizures Using Electroencephalographic Signals," a set of features contributing to discriminate seizure were selected.
The above-cited patents are incorporated by reference.